Preparation of aldehydes or ketones from alcohols

ABSTRACT

A process for preparing an aldehyde or ketone comprising reacting a primary or secondary alcohol with oxygen in the presence of a base, a catalytic amount of a copper salt and a suitable lignad under anhydrous conditions.

The present invention concerns a catalytic oxidative process forpreparing aldehydes or ketones from alcohols. Aldehydes and ketones areimportant intermediates and products in the chemical industry.

The oxidation of certain alcohols to aldehydes or ketones using twoequivalents of copper (I) chloride, an amine, oxygen and potassiumcarbonate is disclosed in Tetrahedron Letters (1977) No.14 1215-8 andTetrahedron (1980) 36 1191-4.

The present invention provides a process for preparing an aldehyde orketone comprising reacting a primary or secondary alcohol with oxygen inthe presence of a base, a catalytic amount of a copper salt and asuitable ligand under anhydrous conditions.

In one particular aspect the present invention provides a process forpreparing an aldellyde or ketone comprising reacting a primary orsecondary alcohol with oxygen in the presence of a base, a productobtainable by mixing a catalytic amount of a copper salt and a suitableligand; the process being conducted under anhydrous conditions.

In another aspect the present invention provides a process for preparingan aldehyde or ketone of formula (I), wherein R¹ is hydrogen, optionallysubstituted alkyl, optionally substituted cycloalkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl; R² is optionallysubstituted alkyl, optionally substituted cycloalkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl, optionally substitutedarylcarbonyl or optionally substituted heteroarylcarbonyl; or R¹ and R²join to form an optionally substituted carbocyclic ring or an optionallysubstituted heterocyclic ring; comprising reacting an alcohol of formula(II), wherein R¹ and R² are as defined above, with oxygen in thepresence of a base, a catalytic amount of a copper salt and a suitableligand under anhydrous conditions.

The suitable ligand is a ligand suitable for copper. The ligand ispreferably an amine. It is preferably a bidentate ligand such as1,10-phenanthroline, a substituted 1.10-phenanthroline (for example5-nitro- 1,10-phenanthroline, 5-chloro-1,10-phenanthroline or5,6-dioxo-1,10-phenanthroline), a pyridine derivative (such as2,2'-bipyridine, 4,4'dimethyl-2-2'-bipyridine, 4,4'-bipyridine,2,2':6',2"-terpyridine or 2,2'-dipyridylamine) or a diamine (such asN,N,N,N-tetrametlhylethiylenediamine or ethyleniediamine).

Oxygen can be supplied in pure form or in the form of air.

It is preferred that the base is a salt such as a carbonate,bicarbonate, alkoxide (provided it is not oxidisable under the reactionconditions, for example tert-butoxide) or acetate of a metal (such as analkali metal or a transition metal having an atomic number of 21-30).Preferred bases are potassium carbonate, potassium acetate, potassiumtert-butoxide, caesium carbonate and sodium carbonate.

A catalytic amount of a copper salt in a sub-stoichiometric amount,preferably 0.9 equivalents or less, more preferably 0.5 equivalents orless. It is preferred that the molar ratio of copper salt:ligand isabout 1:1.

In one particular aspect the present invention provides a processwherein the molar ratio of alcohol of formula (II):copper salt:ligand isin the range 1:(0.01-0.10):(0.01-0.10), especially about 1:0.05:0.05.

It is preferred that the copper salt is a copper (I) salt. Preferredcounter ions are triflate, acetate, cyanide and, especially, chloride.

The copper salt and ligand interact to form a complex. Thus, in afurther aspect the present invention provides a process for preparing analdehyde or ketone comprising reacting a primary or secondary alcoholwith oxygen in the presence of a base and a complex of a copper salt anda suitable ligand; the process being conducted under anhydrousconditions.

In a still further aspect the present invention provides a process forpreparing a compound of formula (I), as hereinbefore defined, theprocess comprising reacting a compound of formula (II), as hereinbeforedefined, with oxygen in the presence of a base and a complex of a coppersalt and a suitable ligand; the process being conducted under anhydrousconditions.

The process of the present invention is preferably carried out in thepresence of a solvent. Suitable solvents include aromatic solvents (suchas benzene, toluene, p-xylene, fluorobenzene, perfluorobenzene,iso-butyl benzene or mesitylene), nitrites (such as acetonitrile),hydrocarbon solvents (such as petroleum fractions), halogenated solvents(such as dichloromethane, tetrachloroethylene or 1,2-dichloroethane) oresters (such as methyl or ethyl acetate). Preferred solvents arearomatic solvents (such as toluene, p-xylene, iso-butyl benzene ormesitylene) or hydrocarbon solvents (such as petroleum fractions).

The process of the present invention is carried out under anhydrousconditions, that is, water that is produced as a by-product of theprocess is either removed from the process environment (such as byazeotropic removal, for example using a Dean and Stark, or similar,apparatus) or the process is conducted in the presence of a drying agent(such as potassium carbonate, magnesium sulphate, sodium sulphate ormolecular sieves).

It is preferred that the process of the invention is carried out atelevated temperature, such as in the range 30-140° C., particularly30-110° C., especially 60-110° C., for example 70-90° C.

The process of the present invention can be carried out at atmosphericpressure, at elevated pressure of up to 10 atmospheres or at autogenicpressure.

Alkyl groups and alkyl moieties have straight or branched chains and,unless stated otherwise, preferably contain from 1 to 24 carbon atoms.Alkyl is, for example, methyl, ethyl, n-propyl, iso-propyl ortert-butyl. Preferred substituents on alkyl groups or moieties includehalogen, alkoxy, haloalkoxy, alkylthio, haloalkylthio, cycloalkyl,cyano, nitro, -NRR³ R⁴, --NHCOR³, --CONR³ R⁴, --COOR³ or --COR³ in whichR³ and R⁴ are independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl orbenzyl, the phenyl and benzyl groups being optionally substituted withhalogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.

Alkenyl groups have straight or branched chains and, unless statedotherwise, preferably contain from 2 to 24, especially from 2 to 10,carbon atoms. The alkenyl groups contain one or more (preferably 1, 2, 3or 4) double bonds. Preferred substituents on alkenyl groups includehalogen, cycloalkyl, optionally substituted aryl or optionallysubstituted heteroaryl.

Alkynyl groups have straight or branched chains and, unless statedotherwise, preferably contain from 2 to 24, especially from 2 to 10,carbon atoms. The alkynyl groups contain one or more (preferably 1 or 2)triple bonds. Preferred substituents on alkynyl groups includecycloalkyl, optionally substituted aryl or optionally substitutedheteroaryl.

Halogen includes bromine and iodine but is preferably chlorine orfluorine.

Cycloalkyl groups preferably contain from 3 to 7 carbon atoms.Cycloalkyl is, for example, cyclohexyl. Cycloalkyl groups are optionallysubstituted by halogen or C₁₋₄ alkyl.

When R¹ and R² join to form a carbocyclic ring it is preferred that thecarbocyclic ring contains 3-9, especially 3-6, carbon atoms and is, forexample, a cyclohexane ring. Alternatively, and when R¹ and R² are in acompound of formula (II), R¹ and R² may join to for an aromaticcarbocyclic ring which is changed to a non-aromatic ring in the compoundof formula (I) as a consequence of the process of the invention.Carbocyclic rings may be fused to one or two optionally substituted arylor optionally substituted heteroaryl groups.

When R¹ and R² join to form a carbocyclic ring (preferably acyclohexane, cyclopentane or cyclohexene ring) that ring, may be part ofan optionally substituted steroid residue. Thus, compounds of formula(II) include, for example, hydrocholesterol, cholesterol, stigmasterol,ergosterol, diosgenin, anosterol, β-sitosterol, lanosterol, euphol,meldenin, digitoxigenin, inokosterone, ecdysone, artenol and fusisterol;alcohols of gonane, oestrane, androstane, pregnane, cholane andcholestane; and reduced derivatives thereof

When R¹ and R² join to form a heterocyclic ring it is preferred that thering contains 3-9 (for example 5, 6 or 7), especially 3-6, atomsselected from the group comprising carbon, nitrogen, sulphur and oxygen.The heterocyclic ring may be fused to one or two optionally substitutedaryl or optionally substituted heteroaryl groups. It is preferred thatthe heterocyclic ring, comprises 1, 2 or 3 nitrogen, sulphur or oxygenatoms. The heterocyclic ring is, for example, pyrrolidine, piperidine,indoline, morpholine, piperazine, a reduced azepine, oxazole, a reducedpyrimidine, a reduced triazine or a reduced triazole.

The carbocyclic and heterocyclic rings are optionally substituted withone or more of halogen, optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted aryl, optionally substitutedheteroaryl, optionally substituted aryl(C₁₋₄)alkyl, optionallysubstituted heteroaryl(C₁₋₄)alkyl, optionally substitutedaryloxy(C₁₋₄)alkyl, optionally substituted heteroaryloxy(C₁₋₄)alkyl oroptionally substituted non-aromatic heterocycle.

Aryl includes naphtlhyl and phenyl.

Aryl, heteroaryl, phenyl or non-aromatic heterocycle groups can beoptionally substituted with one or more of the following: halogen, C₁₋₄alkyl (especially methyl and ethyl), C₂₋₄ alkenyl (especially allyl),C₂₋₄ alkynyl (especially propargyl), C₁₋₄ alkoxy (especially methoxy),C₂₋₄ alkenyloxy (especially allyloxy), C₂₋₄ alkynyloxy (especiallypropargyloxy), halo(C₁₋₄)alkyl (especially trifluoromethyl),halo(C₁₋₄)alkoxy (especially trifluoromethoxy), C₁₋₄ alkylthio(especially methylthio), halo(C₁₋₄)alkylthio, C₁₋₄ alkoxy(C₁₋₄)alkyl,C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, optionally substitutedmethylenedioxy (especially optionally substituted with fluorine or C₁₋₄alkyl), optionally substituted aryl (especially optionally substitutedphenyl), optionally substituted aryloxy (especially optionallysubstituted phenoxy), optionally substituted aryl(C₁₋₄)alkyl (especiallyoptionally substituted benzyl, optionally substituted phenethyl andoptionally substituted phenyl n-propyl), optionally substitutedaryl(C₂₋₄)alkenyl (especially optionally substituted phenylethenyl),optionally substituted aryl(C₁₋₄)alkoxy (especially optionallysubstituted benzyloxy), optionally substituted aryloxy(C₁₋₄)alkyl(especially phenoxymethyl), acyloxy (including C₁₋₄ alkanoyloxy(especially acetyloxy) and benzoyloxy), cyano, thiocyanato, nitro,--NR'R", --NHCOR', --NHCONR'R", --CONR'R", --COOR', --OSO₂ R', --SO₂ R',--COR', --CR'=NR" or --N=CR'R" in which R' and R" are independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groupsbeing optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy; ortwo substituents, when they are in adjacent positions on the aryl ringcan join to form a fused aliphatic ring (especially to form a fused6-membered carbon aliphatic ring).

Substituents which may be present in the aryl ring of any of theforegoing substituents include one or more of the following: halogen,C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ alkoxy, C₂₋₄ alkenyloxy,C₂₋₄ - alkynyloxy, halo(C₁₋₄)alkyl, halo (C₁₋₄)alkoxy, C₁₋₄ alkylthio,C₁₋₄ alkoxy(C₁₋₄)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl,alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, --NR'R", --NHCOR',--NHCONR'R", --CONR'R", --COOR', --SO₂ R', --OSO₂ R', --COR', --CR'=NR"or --N=CR'R" in which R' and R" have the meanings given above.

Heteroaryl rings are preferably 5 or 6-membered ring systems comprising1, 2 or 3 oxygen, sulphur or nitrogen atoms. Heteroaryl is, for example,furan, thiophen, pyridine, pyrimidine, pyrrole, pyrazole, quinoline,isoquinoline, 1,2,4-triazole, imidazole, a triazine (1,2,3-, 1,2,4- or1,3,5-), oxadiazole, thiadiazole, oxazole, thiazole or isoxazole.

Non-aromatic heterocycle includes azetidine, pyrrolidine, piperidine ormorpholine.

In yet another aspect the present invention provides a process forpreparing an aldehyde or ketone of formula (I), wherein R' is hydrogen,optionally substituted alkyl, optionally substituted cycloalkyl,optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl; R² is optionallysubstituted alkyl, optionally substituted cycloalkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl, optionally substitutedarylcarbonyl or optionally substituted heteroarylcarbonyl; or R¹ and R²join to form an optionally substituted carbocyclic ring or an optionallysubstituted heterocyclic ring; comprising reacting an alcohol of formula(II), wherein R¹ and R² are as defined above, with oxygen in thepresence of a base, a product obtainable by mixing a catalytic amount ofa copper salt and a suitable ligand; the process being conducted underanhydrous conditions.

In a further aspect the present invention provides a process asdescribed above wherein R¹ is hydrogen, alkyl or optionally substitutedaryl; and R² is alkyl, alkenyl optionally substituted by phenyl,optionally substituted aryl, optionally substituted heteroaryl oroptionally substituted arylcarbonyl; or R¹ and R² join to form acarbocyclic ring optionally substituted with alkyl or alkenyl.

In a still further aspect the present invention provides a process forpreparing an aldehyde or ketone of formula (I), wherein R¹ is hydrogen,optionally substituted alkyl, optionally substituted cycloalkyl,optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl; R² is optionallysubstituted alkyl, optionally substituted cycloalkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl, optionally substitutedarylcarbonyl or optionally substituted heteroarylcarbonyl; or R¹ and R²join to form an optionally substituted carbocyclic ring or an optionallysubstituted heterocyclic ring; the process comprising reacting analcohol of formula (II), wherein R¹ and R² are as defined above, withoxygen in the presence of a base, a catalytic amount of a copper salt, asuitable ligand and a reducing agent under anhydrous conditions.

In another aspect the present invention provides a process for preparinga compound of formula (I) wherein R¹ is hydrogen, alkyl or optionallysubstituted aryl; and R² is alkyl, alkenyl optionally substituted byphenyl, optionally substituted aryl, optionally substituted heteroarylor optionally substituted arylcarbonyl; or R¹ and R² join to form acarbocyclic ring optionally substituted with alkyl or alkenyl; theprocess comprising reacting an alcohol of formula (II), with oxygen inthe presence of a base, a catalytic amount of a copper salt, a suitableligand and a reducing agent under anhydrous conditions.

In yet another aspect the present invention provides a process forpreparing an aldehyde or ketone of formula (I), wherein R¹ is hydrogen,optionally substituted alkyl, optionally substituted cycloalkyl,optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted aryl, optionally substituted heteroaryl,optionally substituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl; R² is optionallysubstituted alkyl, optionally substituted cycloalkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl, optionally substitutedarylcarbonyl or optionally substituted heteroarylcarbonyl; or R¹ and R²join to form an optionally substituted carbocyclic ring, or anoptionally substituted heterocyclic ring; the process comprisingreacting an alcohol of formula (II), wherein R¹ and R² are as definedabove, with oxygen in the presence of a base, a reducing agent, aproduct obtainable by mixing a catalytic amount of a copper salt and asuitable ligand; the process being conducted under anhydrous conditions.

Suitable reducing agents include hydrazine or a derivative thereof (suchas a 1,2 dicarb(C₁₋₄)alkoxyhydrazine (for example1,2-dicarbethoxyhydrazine, 1,2-dicarbmethoxyhydrazine or1,2-dicarb-tert-butoxyhydrazine), (2,4-dinitrophenyl)hydrazine,tosylhydrazine or an alkylhydrazine (for example dimethylhydrazine)), ora compound which produces a hydrazine under the reaction conditions(such as a di(C₁₋₄ alkyl)diazodicarboxylate, for example diethyldiazodicarboxylate, dimethyl diazodicarboxylate or di-tert-butyldiazodicarboxylate). It is preferred that the molar ratio of reducingagent:copper salt is 1:(0.5-4.0), especially 1:(0.9-2.5), for exampleabout 1:1 or about 1:2.

In another aspect the present invention provides a process for preparinga compound of formula (I) as hereinbefore defined, the processcomprising, reacting an alcohol of formula (II), with oxygen in thepresence of a drying agent (such as potassium carbonate or molecularsieves), a base (such as potassium carbonate or potassiumtert-butoxide), a catalytic amount of a copper (I) salt (such as copper(I) chloride), a suitable ligand (such as 1,10-phenanthroline) and areducing agent (such as 1,2-dicarbethoxyhydrazine).

In a further aspect the present invention provides a process ashereinbefore described for preparing a compound of formula (I) whereinR¹ is hydrogen, C₁₋₂₄ alkyl or phenyl; R² is C₁₋₂₄ alkyl, C₂₋₂₄ alkenyl,C₂₋₂₄ alkenyl substituted with a phenyl group, pyridyl, furyl, thienylor benzoyl; or R¹ and R² join to form a carbocyclic ring optionallysubstituted with alkyl; phenyl groups of the foregoing being optionallysubstituted by halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, C₂₋₄alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy(C₁₋₄)alkyl, cyano ornitro.

The process of the present invention is preferably conducted by mixing acatalytic amount of a copper salt and suitable ligand in an organicsolvent and then adding a drying agent, base, alcohol and, whereappropriate, a reducing agent. Oxygen or air is then bubbled into thereaction mixture and the reaction mixture is heated. Once the processhas (,one to completion the product can be separated by either:

neutralising the reaction mixture with an acid (preferably a strongmineral acid such as hydrochloric acid), and separating the organicphase which contains the product; or,

filtrating the reaction mixture and washing the residue to leave thefiltrate which contains the product.

The following Examples illustrate the process of the invention.

EXAMPLE 1

This Example illustrates the preparation of p-chlorobenzaldehyde.

To a stirred mixture of toluene (12 ml) and copper (I) chloride (12.5mg) were added 1,10-phenanthroline (24 mg), powdered 4 Å sieves (1 g,ex-Fluka, flame-dried), potassium tert-butoxide (0.28 g),1,2-dicarbethoxyhydrazine (0.11 g) and p-chlorobenzyl alcohol (0.36 g).Oxygen was bubbled into the reaction mixture and the reaction mixturewas stirred at 80° C. Ater 45 minutes at 80° C. analysis showed 100%conversion of p-chlorobenzyl alcohol to p-chlorobenzaldehyde.

EXAMPLE 2

This Example illustrates the preparation of p-chlorobenzaldehyde.

To a stirred mixture of toluene (600 ml) and copper (I) chloride (1.24g) was added 1,10-phenanthroline (2.26 g). A complex was allowed toform, as a black-grey solid, before potassium carbonate (70 g) wasadded, followed by 1,2-dicarbethoxyhydrazine (11 ) and thenp-chlorobenzyl alcohol (35.6 g). This was heated to 80-90° C. and gentlecurrent of air was added via a sintered inlet. Aliquots of the solutionwere taken at intervals and analysed by ¹ H NMR spectroscopy. Thereaction was judged to be complete at 5 h, and was allowed to cool. Thecrude reaction mixture was transferred to a 11 separating funnel anddilute hydrochloric acid was added slowly until the aqueous phase wasacidic. The aqueous layer was extracted with toluene (2×100 ml); thecombined organic layers washed with saturated aqueous sodium bicarbonate(100 ml) and brine (100 ml) and dried (MgSO₄). The solvent wasevaporated to leave 34.1 g of a sticky black oil; purity of product (¹ HNMR˜85%). The residue was re-crystallised from ethanol-water (3:1) togive p-chlorobenzaldehyde.

EXAMPLE 3

This Example illustrates the preparation of citral.

Following the procedure of Example 2 but using geraniol in place ofp-chlorobenzyl alcohol and 5 mol % of copper (I) chloride and1,10-phenanthroline gave the title compound in 80% conversion (by ¹ HNMR analysis) after 6 hours.

EXAMPLE 4

This Example illustrates the preparation of acetophenone.

Following the procedure of Example 2 but using 1-phenylethanol in placeof p-chlorobenzyl alcohol and 5 mol % copper (I) chloride and1,10-phenanthroline gave the title compound in 100% conversion (by ¹ NMRanalysis) after 1 hour.

Using similar methodology C₆ H₅ CH(OH)CF₃ was converted to C₆ H₅C(O)CF₃.

EXAMPLE 5

This Example illustrates the preparation of cinnamyl aldehyde.

Following the procedure of Example 2 but using cinnamyl alcohol in placeof p-chlorobenzyl alcohol and 5 mol % copper (I) chloride and1,10-phenantliroline gave the title compound in 100% conversion (by ¹ HNMR analysis) after 1 hour.

EXAMPLE 6

This Example illustrates the preparation of benzil.

Following the procedure of Example 2 but using benzoin in place ofp-chlorobenzyl alcohol and 5 mol % copper (I) chloride and1,10-phenantholine gave the title compound in 100% conversion (by ¹ HNMR analysis) after 3 hours.

EXAMPLE 7

This Example illustrates the preparation of 4-tert-butyl-cyclohexanone.

Following the procedure of Example 2 but usingtrans-4-tert-butylcyclohexanol in place of p-chlorobenzyl alcohol and 20mol % copper (I) chloride and 1,10-phenanthroline gave the titlecompound in 60% conversion (by ¹ H NMR analysis) after 4 hours.

EXAMPLE 8

This Example illustrates the preparation of 4-tert-butylcyclohexanone.

Following the procedure of Example 7 but usingcis-4-tert-butylcyclohexanol in place of trans-4-tert-butylcyclohexanolgave the title compound in 70% conversion (by ¹ H NMR analysis) after 4hours.

EXAMPLE 9

This Example illustrates the preparation of 5-undecanone.

Following the procedure of Example 7 but using 5-undecanol in place oftrans-4-tert-butyl-cyclohexanol gave the title compound in 90%conversion (by ¹ H NMR analysis) after 16 hours.

EXAMPLE 10

This Example illustrates the preparation of 2-undecanone.

Following the procedure of Example 2 but using 2-undecanol in place ofp-chlorobenzyl alcohol and 33 mol % copper (I) chloride and1,10-phenanthroline gave the title compound in 44% conversion (by ¹ NMRanalysis) after 6 hours.

EXAMPLE 11

This Example illustrates the preparation of p-chlorobenzaldehyde.

A solution of anhydrous hydrazine was prepared from a commercialsolution of hydrazine by azeotropic distillation with toluene, to givean approximately 1M solution. Following the procedure of Example 2 usinghydrazine in toluene (12 ml, 1M), copper (I) chloride (12.5 mg),1,10-phenanthroline (24 mg), potassium carbonate (0.7 g), andp-chlorobenzyl alcohol (0.36 g). The reaction was stirred at 80° C. andafter 2 hours ¹ H NMR analysis showed 100% conversion to the titlecompound.

EXAMPLE 12

This Example illustrates the preparation of 2-pyridinecarboxaldehyde.

Copper (I) chloride (12.5 mg) and 1,10-phenanthroline (24 mg) were addedto toluene (12 ml) with stirring. Potassium carbonate (0.7 g),1,2-dicarbethoxyhydrazine (0.11 g) and pyridine-2-methanol (0.27 g) werethen added to the reaction mixture. Oxygen was bubbled into the mixtureand the mixture was stirred at 80° C. for 4 hours. ¹ H NMR analysis ofthe reaction mixture showed a 94% conversion to the title compound.

EXAMPLE 13

This Example illustrates the preparation of 2-thiophenecarboxaldehyde.

Following the procedure of Example 12 but using thiophen-2-methanol inplace of pyridine-2-methanol gave the title compound in 100% conversion(¹ H NMR analysis) after 1 hour.

EXAMPLE 14

This Example illustrates the preparation of 2-furancarboxaldehyde.

Following the procedure of Example 12 but using furfuryl alcohol inplace of pyridine-2-methanol gave the title compound in 100% conversion(¹ H NMR analysis) after 2 hours.

EXAMPLE 15

This Example illustrates the preparation of p-chlorobenzaldehyde.

Copper (I) chloride (12.5 mg) and 1,10-phenanthroline (24 mg) weresuspended in toluene (12 ml) in a flask equipped with a Dean and Starkapparatus. 1,2-Dicarbethoxyhydrazine (0.11 g), potassium tert-butoxide(28 mg) and p-chlorobenzylalcohol (0.36 g) were then added to thereaction mixture. Oxygen was bubbled into the mixture and the mixturewas stirred at reflux. ¹ H NMR analysis of the reaction mixture showed100% conversion to the title compound after 3 hours.

EXAMPLE 16

This Example illustrates the preparation of p-chlorobenzaldehyde.

Copper (I) chloride (12.5 mg) and 1,10-phenantliroline (24 mg) weresuspended in toluene (12 ml). Potassium carbonate (0.7 g), diethyldiazodicarboxylate (0.11 g) and p-chlorobenzylalcohol (0.36 g) wereadded sequentially to the reaction mixture. Oxygen was bubbled into themixture and the mixture was stirred at reflux. ¹ H NMR analysis of thereaction mixture showed 100% conversion to the title compound after 0.5hours.

EXAMPLE 17

This Example illustrates the preparation of p-chlorobenzaldehyde.

Copper (I) chloride (10 mg) and 1,10-phenanthroline (18 mg) weresuspended in toluene (5 ml). 4 Å molecular sieves, di-tert-butyldiazodicarboxylate (0.276 g) and p-chlorobenzylalcohol (0.143 g) wereadded successively and the resulting mixture was stirred for 12 hours atroom temperature whilst oxygen was bubbled in. After dilution withdiethyl ether (10 ml), the reaction mixture was filtered and thefiltrate evaporated in vacuo to leave the title compound in 99% yieldand 100% conversion.

EXAMPLE 18

This Example illustrates the preparation of p-chlorobenzaldehyde.

To a mixture of copper (I) chloride (1.98 g) and 1,10-phenanthroline(3.60 g) were added toluene (800 ml) and potassium carbonate (110 g).The resulting mixture was stirred for 30 minutes after whichdi-tert-butyl azodicarboxylate (4.60 g) and p-chlorobenzylalcohol (57.0g) were added successively. The mixture was heated to 90° C. and oxygengas was bubbled in for 1.5 hours. After cooling to room temperature thereaction mixture was diluted with diethyl ether (500 ml) and filteredthrough a pad of CELITE™. The filtrate was washed successively withwater (200 ml), 1N aqueous hydrochloric acid (200 ml) and brine (200ml), dried over magnesium sulphate and evaporated in vacuo. Theresulting residue was distilled to provide the title compound (46.5 g,83% yield).

EXAMPLES 19-39

The following procedure was followed for Examples 19-39.

Toluene (10 ml) was added to a mixture of copper (I) chloride (0.10mmol, 5 mol % to alcohol) and 1,10-phenanthroline (0.10 mmol, 5 mol % toalcohol). The mixture was stirred at of room temperature for 10 minutesand a black-grey precipitate formed. To this were added successivelypotassium carbonate (4.00 mmol, 200 mol % to alcohol), a reducing agent1,2-dicarb-tert-butoxyhydrazine (DBAD-H₂) or di-tert-butyldiazodicarboxylate (DBAD)! (0.10 mmol, 5 mol % to alcohol) and a primaryor secondary alcohol (2.00 mmol). The resulting mixture was heated to90° C. and oxygen was bubbled in for a period of time (T). The reactionmixture was then cooled to room temperature, diluted with diethyl ether(10 ml) and filtered through a pad of CELITE™. The filtrate was filteredin vacuo and the residue purified by silica gel column chromatography(eluting with ethyl acetate:hexane 1:10-1:5) to provide aldehyde orketone.

Results for Examples 19-39 are provided in the Table below.

    ______________________________________                                         Con-    Exam-                                ver-    ple                    Reducing      sion Yield    No    Alcohol          Agent    T    (%)  (%).sup.3    ______________________________________    19    p-Chlorobenzyl alcohol                           DBAD-H.sub.2                                    0.75 100  90    20.sup.b          p-Chlorobenzyl alcohol                           DBAD     1    100  83.sup.c    21    Cinnamyl alcohol DBAD-H.sub.2                                    1    100  89    22    Cinnamyl alcohol DBAD     1    100  80    23    Geraniol         DBAD-H.sub.2                                    1     75  67    24.sup.d          Geraniol         DBAD-H.sub.2                                    1     86  74    25    Geraniol         DBAD     1     74  71    26    Nerol            DBAD-H.sub.2                                    1     83  73    27    1-Decanol        DBAD-H.sub.2                                    0.75  80.sup.c                                              63.sup.c    28.sup.d          1-Decanol        DBAD-H.sub.2                                    0.75  87.sup.c                                              72.sup.c    29    1-Decanol        DBAD     0.75  74.sup.c                                              58.sup.c    30    2-Undecanol      DBAD-H.sub.2                                    2     86  86    31    2-Undecanol      DBAD     2     90  88    32    4-tert-Butylcyclohexanol                           DBAD-H.sub.2                                    2     59  57    33.sup.f          4-tert-Butylcyclohexanol                           DBAD-H.sub.2                                    2     71  68    34.sup.d          4-tert-Butylcyclohexanol                           DBAD-H.sub.2                                    2     80  76    35.sup.g          4-tert-Butylcyclohexanol                           DBAD     2     87  84    36.sup.g          Hydrocholesterol DBAD     2     74  70    37    p-(Methylthio)benzyl alcohol                           DBAD-H.sub.2                                    1     95  92    38    3-Pyridylcarbinol                           DBAD-H.sub.2                                    1     92  81    39    α-Trifluoromethyl-2-                           DBAD     1     99  92          naphthalenemethanol    ______________________________________     a = isolated yield unless otherwise noted     b = reaction carried out on 0.4 mol scale     c = determined after distillation     d = copper (I) chloride, 1,10phenanthroline and DBADH.sub.2 used at 10 mo     % to alcohol     e = determined by gas chromatography using tetradecane as internal     standard     f = DBADH.sub.2 used at 10 mol % to alcohol     g = copper (I) chloride, 1,10phenanthroline and DBAD used at 10 mol % to     alcohol     ##STR1##

We claim:
 1. A process for preparing an aldehyde or ketone of formula(I): wherein R¹ is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl,heteroaryl, aryl(C₁₋₄ l )alkyl, heteroaryl(C₁₋₄)alkyl,aryloxy(C₁₋₄)alkyl, heteroaryloxy(C₁₋₄)alkyl; R² is alkyl cycloalkyl,alkenyl, alkynyl, aryl, heteroaryl, aryl(C₁₋₄)alkyl,heteroaryl(C₁₋₄)alkyl, aryloxy(C₁₋₄)alkyl, heteroaryloxy(C₁₋₄)alkyl,arylcarbonyl or heteroarylcarbonyl; or R¹ and R² join to form acarbocyclic ring or a heterocyclic ring; carbocyclic and heterocyclicrings are optionally substituted with one or more of halogen, optionallysubstituted alkyl, optionally substituted alkenyl, optionallysubstituted aryl, optionally substituted heteroaryl, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substitutedheteroaryl(C₁₋₄)alkyl, optionally substituted aryloxy(C₁₋₄)alkyl,optionally substituted heteroaryloxy(C₁₋₄)alkyl or optionallysubstituted non-aromatic heterocycle; alkyl groups or moieties areoptionally substituted by halogen, alkoxy, haloalkoxy, alkylthio,haloalkylthio, cycloalkyl, cyano, nitro, --NR³ R⁴, --NHCOR³, --CONR³ R⁴,--COOR³ or --COR³ in which R³ and R⁴ are independently hydrogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groupsbeing optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy;alkenyl groups are optionally substituted by halogen, cycloalkyl,optionally substituted aryl or optionally substituted heteroaryl;alkynyl groups are optionally substituted by cycloalkyl, optionallysubstituted aryl or optionally substituted heteroaryl; cycloalkyl groupsare optionally substituted by halogen or C₁₋₆ alkyl; aryl, heteroaryl,phenyl or non-aromatic heterocycle groups are optionally substitutedwith one or more of the following: halogen, C₁₋₄ alkyl, C₂₋₄ alkenyl,C₂₋₄ alkynyl, C₁₋₄ alkoxy, C₂₋₄ alkenyloxy, C₂₋₄ alkynyloxy,halo(C₁₋₄)alkyl, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, halo(C₁₋₄)alkylthio,C₁₋₄ alkoxy(C₁₋₄)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl,methylenedioxy (optionally substituted with fluorine or C₁₋₄ alkyl),optionally substituted aryl, optionally substituted aryloxy, optionallysubstituted aryl(C₁₋₄)alkyl, optionally substituted aryl(C₂₋₄)alkenyl,optionally substituted aryl(C₁₋₄)alkoxy, optionally substitutedaryloxy(C₁₋₄)alkyl, acyloxy, cyano, thiocyanato, nitro, --NR'R",--NHCOR', --NHCONR'R", --CONR'R", --COOR', --OSO₂ R', --SO₂ R', --COR',--CR'=NR" or --N=CR'R"; or two substituents, when they are in adjacentpositions on the aryl ring can join to form a fused aliphatic ring;substituents which may be present in the aryl ring of any of theforegoing substituents include one or more of the following: halogen,C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C,₁₋₄ alkoxy, C₂₋₄ alkenyloxy,C₂₋₄ alkynyloxy, halo(C₁₋₄)alkyl, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₁₋₄alkoxy(C₁₋₄)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl,alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, --NR'R", --NHCOR,--NHCONR'R", --CONR'R", --COOR', --SO₂ R', --OSO₂ R', --COR', --CR'=NR"or --N=CR'R"; R' and R" are independently hydrogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl,phenyl or benzyl, the phenyl and benzyl groups being optionallysubstituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy; the processcomprising reacting an alcohol of formula (II): ##STR2## wherein R¹ andR² are as defined above, with oxygen in the presence of:i. as a base: acarbonate, bicarbonate, alkoxide (provided it is not oxidisable underthe reaction conditions) or acetate of an alkali metal or a transitionmetal having an atomic number of 21-30; ii. a catalytic amount of acopper (I) salt; and, iii. as a bidentate ligand: 1,10-phenanthroline, asubstituted 1,10-phenanthroline, a pyridine derivative or adiamine;under anhydrous conditions.
 2. A process as claimed in claim 1wherein the process is carried out in the presence of a reducing agent.3. A process as claimed in claim 2 wherein the copper salt is copper (I)chloride.
 4. A process as claimed in claim 2 wherein the molar ratio ofalcohol of formula (II):copper (I) salt:ligand is in the range1:(0.01-0.10):(0.01-0.10).
 5. A process as claimed in claim 2 whereinthe molar ratio of copper (I) salt:ligand is about 1:1.
 6. A process asclaimed in claim 2 wherein the process is carried out in a solvent.
 7. Aprocess as claimed in claim 1 wherein the process is carried out in asolvent.
 8. A process as claimed in claim 1 wherein the copper salt iscopper (I) chloride.
 9. A process as claimed in claim 2 wherein thereducing agent is a hydrazine or derivative thereof, or a compound thatproduces a hydrazine under the reaction conditions.
 10. A process asclaimed in claim 1 wherein the molar ratio of alcohol of formula(II):copper (I) salt:ligand is in the range 1:(0.01-0.10):(0.01-0.10).11. A process as claimed in claim 1 wherein the molar ratio of copper(I) salt:ligand is about 1:1.